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Cardiomyocytes in Hypoxia: Cellular Responses and Implications for Cell-Based Cardiac Regenerative Therapies
Kiera D Dwyer1, Caroline A Snyder1, Kareen L K Coulombe1
1Institute for Biology, Engineering, and Medicine, School of Engineering, Brown University, Providence, RI 02912, USA.
Insights
Stem cell-derived cardiomyocytes (SC-CMs) face oxidative stress after myocardial infarction (MI). Enhancing SC-CMs
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Cellular Biology
Background:
- Myocardial infarction (MI) causes significant cardiomyocyte loss and limited cardiac regeneration.
- Cell-based therapies using stem cell-derived cardiomyocytes (SC-CMs) aim to restore heart function post-MI.
- The ischemic environment of the infarcted heart poses oxidative stress challenges to implanted SC-CMs.
Purpose of the Study:
- To comprehensively review cardiac pathophysiology during and after MI.
- To understand how MI-induced changes define the cardiac environment for cell therapy.
- To explore cell culture strategies for enhancing SC-CMs' resistance to hypoxia.
Main Methods:
- Literature review synthesizing current knowledge on cardiac pathophysiology post-MI.
- Analysis of the cellular, tissue, and organ level changes in the cardiac environment.
- Exploration of cell culture techniques to improve SC-CM resilience.
Main Results:
- Detailed summary of cardiac pathophysiology during and after MI.
- Characterization of the cardiac environment's impact on SC-CMs.
- Identification of potential cell culture strategies to enhance SC-CM hypoxia resistance.
Conclusions:
- Understanding the post-MI cardiac environment is crucial for effective cell-based therapies.
- SC-CMs require enhanced resistance to oxidative stress for successful implantation.
- Engineering robust SC-CMs through optimized cell culture is key for clinical translation.
Abstract:
Myocardial infarction (MI) is a severe hypoxic event, resulting in the loss of up to one billion cardiomyocytes (CMs). Due to the limited intrinsic regenerative capacity of the heart, cell-based regenerative therapies, which feature the implantation of stem cell-derived cardiomyocytes (SC-CMs) into the infarcted myocardium, are being developed with the goal of restoring lost muscle mass, re-engineering cardiac contractility, and preventing the progression of MI into heart failure (HF). However, such cell-based therapies are challenged by their susceptibility to oxidative stress in the ischemic environment of the infarcted heart. To maximize the therapeutic benefits of cell-based approaches, a better understanding of the heart environment at the cellular, tissue, and organ level throughout MI is imperative. This review provides a comprehensive summary of the cardiac pathophysiology occurring during and after MI, as well as how these changes define the cardiac environment to which cell-based cardiac regenerative therapies are delivered. This understanding is then leveraged to frame how cell culture treatments may be employed to enhance SC-CMs' hypoxia resistance. In this way, we synthesize both the complex experience of SC-CMs upon implantation and the engineering techniques that can be utilized to develop robust SC-CMs for the clinical translation of cell-based cardiac therapies.
